Paracrine communication between malignant and non-malignant prostate epithelial cells in culture alters growth rate, matrix protease secretion and in vitro invasion

Epithelial cancer cell invasion is facilitated by stromal cells, immune cells, endothelial cells and other epithelial cells. We have used two human papilloma immortalized prostate cell lines, CA-HPV-10 from a carcinoma and PZ-HPV-7 cells from normal prostatic epithelium to study cell–cell influences on growth, gelatinase secretion, invasion and responses to TGFβ1. We found that co-culture with CA-10 carcinoma cells stimulates proliferation of the PZ-7 epithelial line. TGFβ1 inhibited growth of both lines, but while inhibitory effects on the CA-10 cells diminished after removal of the peptide, inhibition of PZ-7 was lasting. Interestingly, the TGFβ-induced growth inhibition in PZ-7 cells could be partially reversed by co-culture with CA-10 cells. Co-culture with CA cells in a 3-chamber invasion assay also promoted invasion of PZ cells. CA-10 invasion was enhanced by co-culture with TGFβ1-treated-PZ-7 cultures and this enhancement was associated with TGFβ1-induced secretion of matrix metalloproteinase-9. Our observations suggest that interaction between prostate cancer cells and prostate epithelial cells may promote proliferation of the epithelial cell population and produce a paracrine source of MMP-9 which may facilitate early cancer cell invasion.